| P-glycoprotein transporter expression on a549 respiratory epithelial cells is positively correlated with intracellular dexamethasone levels. | |
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MedLine Citation:
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PMID: 20940624 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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BACKGROUND: Several mechanisms of glucocorticoid resistance in asthma have been proposed. P-glycoprotein (P-gp), a ubiquitous efflux transport protein, is associated with variability in the disposition of many drugs and interindividual variability in drug treatment response. This study was undertaken to determine the effect of P-gp expression on glucocorticoid efflux from airway epithelial cells. HYPOTHESIS: Decreasing respiratory epithelial P-gp expression in dexamethasone-exposed airway epithelial cells in vitro will increase intracellular dexamethasone concentration. METHODS: A549 lung epithelial cells, transfected with small interfering RNA (siRNA) targeted at messenger RNA for the gene encoding P-gp, were exposed to 100-nM dexamethasone for 15 minutes. Transfection efficiency of siRNA, P-gp expression, and intracellular dexamethasone were measured with flow cytometry. RESULTS: Cells transfected with both negative siRNA and siRNA targeted at P-gp exhibited a positive correlation of P-gp expression with intracellular dexamethasone. The mean ± SEM correlation coefficients were 0.78 ± 0.07 for cells transfected with negative siRNA and 0.79 ± 0.08 for cells transfected with siRNA targeted at P-gp. DISCUSSION: Contrary to our hypothesis, the positive correlation between P-gp expression and intracellular dexamethasone suggests that P-gp is not a primary transporter of glucocorticoids from airway epithelial cells. Increased P-gp expression is unlikely to be an important mechanism of glucocorticoid resistance in asthma. |
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Authors:
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Joanna S Cohen; Angela S Benton; Fisayo Nwachukwu; Tugba Ozedirne; Stephen J Teach; Robert J Freishtat |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of investigative medicine : the official publication of the American Federation for Clinical Research Volume: 58 ISSN: 1708-8267 ISO Abbreviation: J. Investig. Med. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9501229 Medline TA: J Investig Med Country: Canada |
Other Details:
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Languages: eng Pagination: 991-4 Citation Subset: IM |
Affiliation:
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Center for Genetic Medicine Research, Children's National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010, USA. jcohen@cnmc.org |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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